Laser Ablation Plus Immunotherapy Improves Survival in Recurrent Glioblastoma

Recurrent high-grade astrocytoma, including glioblastoma, is difficult to treat and often returns after surgery. Patients with recurrence typically survive only four to five months, highlighting a critical need for better options. Immune checkpoint inhibitors rarely work in these tumors because the blood–brain barrier blocks effective immune access. To overcome this obstacle, investigators now report that combining a minimally invasive laser-based ablation technique with immunotherapy may extend survival in this difficult-to-treat population.

The strategy, developed at the Keck School of Medicine of the University of Southern California (USC; Los Angeles, CA, USA), integrates laser interstitial thermal therapy (LITT) with the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab. Under magnetic resonance imaging (MRI) guidance, neurosurgeons advance a probe into the lesion and apply controlled laser heat to ablate the tumor while avoiding adjacent brain tissue. LITT also intentionally disrupts the blood–brain barrier, after which patients receive pembrolizumab with the aim of leveraging this window of increased permeability to augment antitumor immune activity.

This transient disruption allows tumor material to enter the bloodstream and exposes tumor antigens to the immune system. Once activated by the checkpoint inhibitor, T cells can more readily traffic back across the temporarily opened barrier to locate and attack residual tumor. The strategy is designed to convert immune-inaccessible brain tumors into targets that respond to systemic immunotherapy.

In a Phase 1/2b clinical trial, 45 patients with recurrent high-grade astrocytoma were enrolled; all were in second recurrence and nearly 15% were in third recurrence. Participants received either LITT or surgery/biopsy, followed by pembrolizumab. Nearly half of those treated with LITT plus pembrolizumab were alive at 18 months, whereas none of the patients given surgery followed by pembrolizumab survived to 18 months. More than one-third of patients in the LITT-plus-pembrolizumab arm lived beyond three years. The combination was generally safe and well tolerated.

Findings were published in Nature Communications on February 26, 2026. Keck Medical Center of USC was one of three U.S. trial sites, along with Washington University in St. Louis and the University of Florida. Since trial initiation, the U.S. Food and Drug Administration (FDA) has cleared LITT for certain brain tumors, and pembrolizumab has been approved for several cancers.

“These results suggest that LITT can help the immune checkpoint inhibitor pembrolizumab work more effectively against high-grade astrocytoma. Patients with this type of advanced cancer have few remaining options and poor outcomes, and this approach could meaningfully extend their survival time and provide new hope for patients and their loved ones,” said David Tran, MD, Ph.D., chief of neuro-oncology with Keck Medicine, co-director of the USC Brain Tumor Center and lead author of the study.

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Keck Medicine of USC